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Biomedical subjects

R L Barbieri

Publications and source records attributed to R L Barbieri.

At least 127 records · Page 7Linked to original sources
PubMed1987

Immunosuppressive effects of danazol in vitro.

The effects of danazol on leukocyte activation in vitro were compared with those of other known immunosuppressive steroids. Danazol at a concentration of 10(-6) M, the systemic level in women taking 600 mg/day, significantly inhibited lymphocyte proliferation in cultures activated by T-cell mitogens (Concanavalin A and phytohemagglutinin) and allogeneic mixed lymphocyte culture (MLC). Comparable immunosuppressive effects were achieved in these assay systems with dexamethasone at a concentration of 10(-8) M, and with cortisol and progesterone at a concentration of 10(-6) M. Physiologic concentrations of estradiol and testosterone did not significantly affect these immunologic test systems. These studies provide evidence that danazol is immunosuppressive. It is possible that immunosuppressive effects contribute to the efficacy of this drug in the treatment of endometriosis and autoimmune disorders.

Analysis of Variance↗
PubMed1986

Decreased fetal cord prolactin concentration in diabetic pregnancies.

Infants of diabetic mothers are known to have a greater incidence of respiratory distress syndrome than normal control infants. Fetal lung maturation is modulated by a large number of hormones. To further investigate a possible role of hormonal modulators of lung maturation in infants of diabetic mothers, fetal cord prolactin, estrone, estradiol, thyroxine, triiodothyronine, and triiodothyronine-resin uptake index levels were measured in infants of diabetic mothers (n = 40) and nondiabetic mothers (n = 40) at term. Infants of diabetic mothers had significantly lower mixed-cord serum prolactin levels (p less than 0.0005) than control infants. There was no significant difference in cord serum thyroxine, triiodothyronine-resin uptake index, triiodothyronine, estrone, or estradiol levels between the infants of diabetic mothers and the infants of control mothers. These findings raise the possibility that decreased fetal prolactin levels may be associated with, or contribute to, the delayed lung maturation reported with diabetic pregnancies.

Amniotic Fluid↗
PubMed1986

Elevated concentrations of the beta-subunit of human chorionic gonadotropin and testosterone in the amniotic fluid of gestations of diabetic mothers.

Hyperplasia of testicular Leydig cells and ovarian theca-lutein cells is a common histologic finding in infants of diabetic mothers. The functional correlates of this histologic finding were investigated by measurement of the beta-subunit of human chorionic gonadotropin, testosterone, dihydrotestosterone, androstenedione, estradiol, and estrone in the amniotic fluid compartment of gestations with male and female fetuses in diabetic mothers (N = 34) and control women (N = 34) at term. When compared with those of control subjects, gestations of diabetic mothers had significantly higher amniotic fluid concentrations of the beta-subunit of human chorionic gonadotropin. Gestations with either male or female fetuses in diabetic mothers had significantly higher amniotic fluid testosterone and dihydrotestosterone levels when compared with those of their respective gender controls. In gestations with male fetuses in diabetic mothers there was a significant positive correlation between the beta-subunit of human chorionic gonadotropin and testosterone. There was no significant difference in amniotic fluid androstenedione, estradiol, or estrone levels between the gestations of diabetic mothers and those of control women. These results suggest that the testicular Leydig cell and ovarian theca-lutein cell hyperplasia seen in infants of diabetic mothers is due, in part, to elevated levels of human chorionic gonadotropin and is associated with elevated testosterone and dihydrotestosterone concentrations in the amniotic fluid.

Amniotic Fluid↗
PubMed1986

Elevated serum concentrations of CA-125 in patients with advanced endometriosis.

CA-125 is a high-molecular-weight glycoprotein that is expressed on the cell surface of some derivatives of embryonic coelomic epithelium. Based on results of an immunoradiometric assay developed to detect CA-125 in peripheral blood, 82% of patients with ovarian cancer and less than 1% of apparently healthy controls have elevated peripheral blood levels of CA-125. Because endometriotic lesions are likely to be derivatives of embryonic coelomic epithelium, the authors investigated serum CA-125 levels in patients with endometriosis. Preoperative serum CA-125 concentrations were measured in 147 patients undergoing diagnostic laparoscopy or laparotomy. Serum CA-125 concentrations were elevated in patients with stage III or IV endometriosis, compared with controls with negative diagnostic laparoscopies (66.5 +/- 14.5 versus 8.20 +/- 0.59 U/ml, mean +/- standard error of the mean; P less than 0.001). Fifty-four percent of patients with stage III or IV endometriosis and 0% of the controls had CA-125 levels greater than 35 U/ml. Occasional patients with stage II endometriosis (13%), leiomyomata uteri (14%), and chronic pelvic inflammatory disease (5%) also had serum CA-125 concentrations greater than 35 U/ml. Immunocytochemical techniques demonstrated the presence of CA-125 on the cell surface of endometriotic lesions.

Adolescent↗
PubMed1986

Nicotine, cotinine, and anabasine inhibit aromatase in human trophoblast in vitro.

Epidemiologic studies suggest that women who smoke have lower endogenous estrogen than nonsmokers. To explore the possible link between cigarette smoking and decreased endogenous estrogens, we have examined the effects of constituents of tobacco on estrogen production in human choriocarcinoma cells and term placental microsomes. In choriocarcinoma cell cultures, nicotine, cotinine (a major metabolite of nicotine), and anabasine (a minor component of cigarette tobacco) all inhibited androstenedione conversion to estrogen in a dose-dependent fashion. Removal of nicotine, cotinine, and anabasine from the culture medium resulted in the complete reversal of the inhibition of aromatase. In the choriocarcinoma cell cultures, a supraphysiologic concentration of androstenedione (73 microM) in the culture medium blocked the inhibition of aromatase caused by nicotine, cotinine, and anabasine. In preparations of term placental microsomes, nicotine, cotinine, and anabasine inhibited the conversion of testosterone to estrogen. Kinetic analysis demonstrated the inhibition to be competitive with respect to the substrate. These findings suggest that some nicotinic alkaloids directly inhibit aromatase. This mechanism may explain, in part, the decreased estrogen observed in women who smoke.

Anabasine↗
PubMed1986

Insulin stimulates androgen accumulation in incubations of ovarian stroma obtained from women with hyperandrogenism.

The effects of insulin and insulin-like growth factors (IGFs) on ovarian androgen production were examined in ovarian stroma obtained from four women with hyperandrogenism and three women without hyperandrogenism. In incubations of stroma obtained from all four hyperandrogenic patients, insulin alone (500 ng/ml) significantly stimulated androstenedione and testosterone release. LH alone (25 ng/ml) significantly stimulated androstenedione release in incubations of stroma obtained from three of the four hyperandrogenic patients and testosterone release in incubations of stroma obtained from one of the four hyperandrogenic patients. In stromal incubations from three of the four hyperandrogenic patients, insulin alone (500 ng/ml) resulted in a significantly greater release of androstenedione and testosterone than did LH alone (25 ng/ml). Dihydrotestosterone was released in measurable quantities in incubations of stromal tissue obtained from three of the four hyperandrogenic women. In all three instances in which dihydrotestosterone was detectable, insulin alone (500 ng/ml), but not LH alone (25 ng/ml), significantly stimulated dihydrostestosterone release. Incubations of stroma obtained from three nonhyperandrogenic, normally cycling women demonstrated low levels of androstenedione release and negligible testosterone and dihydrotestosterone release. Insulin alone (500 ng/ml) and LH alone (25 ng/ml) produced no significant increase in androstenedione release. Insulin (500 ng/ml) plus LH (25 ng/ml) significantly stimulated androstenedione accumulation in stroma obtained from two of the nonhyperandrogenic women. One insulin dose-response experiment was performed using stromal tissue obtained from a hyperandrogenic woman. In this experiment, insulin, at a dose of 50 ng/ml, was as effective as insulin at a dose of 500 ng/ml in stimulating androstenedione and testosterone release. In addition to insulin, IGF-I/somatomedin C (50 ng/ml) stimulated androstenedione and testosterone release. Relaxin (1 microgram/ml) and multiplication-stimulating activity (50 ng/ml) did not stimulate androstenedione and testosterone release. These studies suggest that human ovarian stroma may be a target tissue for insulin and IGF-I, and that hyperinsulinemia may be an important factor contributing to ovarian hyperandrogenism.

Adult↗
PubMed1986

Constituents of cigarette smoke inhibit human granulosa cell aromatase.

Recent epidemiologic studies suggest that women smokers have lower endogenous estrogen levels than nonsmokers. The effects of aqueous extracts of cigarette smoke on aromatase were evaluated in cultures of human granulosa cells. Aqueous extracts of cigarette smoke inhibited the conversion of androstenedione (delta 4A) to estradiol in a dose-dependent manner. Dialysis experiments demonstrated that 90% of the inhibitory activity of aqueous extracts of cigarette smoke was in the less than 1000 mol wt fraction. Removal of the aqueous extract of cigarette smoke from the culture medium resulted in a complete reversal of the inhibition of delta 4A aromatization. Addition of supraphysiologic concentrations of delta 4A (73 microM) to the culture medium blocked the smoke-induced inhibition of aromatization. Two low-molecular-weight components of cigarette smoke, nicotine and anabasine, inhibited granulosa cell aromatase in a dose-dependent manner. These studies suggest that constituents of cigarette smoke inhibit a major steroidogenic pathway.

Anabasine↗
PubMed1985

Prolactin response to thyrotropin-releasing hormone (TRH) in patients with hypothalamic-pituitary disease.

The prolactin (PRL) response to thyrotropin-releasing hormone (TRH) was evaluated in 686 patients over a 4-year period. Of the 170 control subjects tested, none had a blunted PRL response to TRH. Eighty patients with prolactinomas documented by surgery were tested. Ninety-five percent (76 of 80) of these patients had an abnormally blunted PRL response to TRH. Of the 87 patients with a prolactinoma who did not undergo surgery, 98% (85 of 87) had a blunted PRL response to TRH. Many patients with other pituitary and hypothalamic diseases (pituitary tumors other than prolactinomas [Cushing's disease, acromegaly, chromophobe adenoma], craniopharyngioma) also had an abnormal PRL response to TRH (79 of 153, 52%). In the majority of patients with hyperprolactinemia due to dopamine antagonist medications, TRH stimulation did not produce a normal rise in PRL. The TRH test may be helpful in confirming the diagnosis of prolactinoma, but it is not a decisive factor in the diagnosis or management of this entity.

Adenoma↗
PubMed1985

Elevated beta-human chorionic gonadotropin and testosterone in cord serum of male infants of diabetic mothers.

Leydig cell hyperplasia is a common histological finding in male infants of diabetic mothers. The functional correlates of this histological finding were investigated by measuring beta hCG, testosterone, androstenedione, dihydrotestosterone, and progesterone in mixed cord serum of male and female infants of diabetic mothers (n = 40) and normal mothers (n = 40) at term. Male and female infants of diabetic mothers had significantly higher cord serum beta hCG levels than male and female controls. Male infants of diabetic mothers had significantly higher cord serum testosterone concentrations than male controls, female controls, and female infants of diabetic mothers. Cord serum testosterone concentrations were similar in female infants of diabetic mothers and female controls. In the male infants of diabetic mothers, there was a significant positive correlation between beta hCG and testosterone (r = 0.64; P less than 0.01). There was no significant correlation between beta hCG and testosterone in the male controls (r = -0.15; P = NS). There was no significant difference in cord serum dihydrotestosterone in any group tested. Cord serum progesterone was significantly higher in the males than in the females. Cord serum androstenedione was lower in the infants of diabetic mothers than in the controls. This study suggests that the Leydig cell hyperplasia found in male infants of diabetic mothers is due, in part, to elevated concentrations of hCG and is accompanied by elevated testosterone concentrations in the fetal compartment.

Androstenedione↗
PubMed1984

Insulin stimulates androgen accumulation in incubations of human ovarian stroma and theca.

The effects of insulin on ovarian steroidogenesis were examined in four-day incubations of minced stroma and theca obtained from a woman with hyperandrogenism, insulin resistance, and acanthosis nigricans, and from a normally cycling woman. In incubations of theca obtained from the patient with hyperandrogenism, insulin resistance, and acanthosis nigricans, lutenizing hormone (LH) (25 ng/mL) alone stimulated androstenedione, testosterone, progesterone, and estradiol accumulation. Insulin (500 ng/mL) alone stimulated androstenedione and testosterone accumulation, but not progesterone or estradiol accumulation. In incubations of stroma obtained from the hyperandrogenism, insulin resistance, and acanthosis nigricans patient, LH (25 ng/mL) alone stimulated androstenedione and testosterone accumulation, but not dihydrotestosterone accumulation. Insulin (500 ng/mL) alone stimulated androstenedione, testosterone, and dihydrotestosterone accumulation. In incubations of stroma from the normally cycling woman, LH plus insulin acted synergistically to stimulate androstenedione accumulation. These results suggest that insulin may be a regulator of steroid biosynthesis in the thecal and stromal compartments of the human ovary.

Acanthosis Nigricans↗
PubMed1983

Hyperandrogenism, insulin resistance, and acanthosis nigricans syndrome: a common endocrinopathy with distinct pathophysiologic features.

The HAIR-AN syndrome that consists of hyperandrogenism (HA), insulin resistance (IR), and acanthosis nigricans (AN) is an underdiagnosed endocrinopathy, because hyperandrogenic women are not commonly screened for insulin resistance or acanthosis nigricans. The distinct pathophysiologic features of the HAIR-AN syndrome are discussed in detail. In this syndrome, the primary pathophysiologic derangements are the insulin resistance and the hyperandrogenism. The acanthosis nigricans is an epiphenomenon of these primary processes. In patients with the HAIR-AN syndrome, the degree of severity of the insulin resistance is positively correlated with the degree of severity of the hyperandrogenism. In patients with adequate pancreatic beta-islet cell reserve, insulin resistance results in a long-term increase in circulating insulin levels. The hyperinsulinemia probably directly stimulates ovarian androgen production. In turn, hyperandrogenism itself produces insulin resistance. This positive feedback loop between insulin resistance and hyperandrogenism propagates the disease, and increases its severity over time. The relationship between insulin resistance and hyperandrogenism may explain the hyperandrogenemia seen in the following disease processes: obesity, acromegaly, lipoatrophic diabetes, leprechaunism, and Kahn types A and B insulin resistance.

Acanthosis Nigricans↗
PubMed1983

Aromatization of norethindrone to ethinyl estradiol by human placental microsomes.

The interaction of 19-norethindrone [4-estren-17 alpha-ethinyl-17 beta-ol,3-one (NET)] with human placental microsomes was investigated using enzymatic and spectral techniques. The incubation of [6,7-3H]norethindrone with human placental microsomes, NADPH, and molecular oxygen resulted in the production of ethinyl estradiol [1,3,5-(10)estratrien-17 alpha-ethinyl-3,17 beta-diol (EE)]. The reaction was linear with respect to time and protein concentration. Androstenedione inhibited the enzymatic aromatization of NET to EE. The product was identified by thin layer chromatography, recrystallization to constant specific activity, and derivative formation. No acid or base was used in any step of product identification. To ensure that spontaneous aromatization of metabolites of NET did not contribute to our results, representative samples were treated with sodium borohydride before processing. Sodium borohydride reduces the 4-en-3-one grouping of the A-ring, thereby preventing chemical aromatization. Sodium borohydride treatment did not reduce our observed yields of EE from NET. The addition of NET to a preparation of solubilized, partially purified placental microsomal cytochrome P-450 yielded a type I cytochrome P-450 binding spectrum. The apparent spectral dissociation constant for NET binding to cytochrome P-450 was 28 microM. These results suggest that NET is enzymatically aromatized to EE by human placental microsomes.

Borohydrides↗
PubMed1983

Effects of insulin on steroidogenesis in cultured porcine ovarian theca.

The effects of insulin on porcine thecal steroidogenesis were examined in long-term cultures of hyaluronidase-collagenase dispersed thecal cells. The thecal cultures made significant amounts of progesterone (P) and androstenedione (delta 4 A). Testosterone, dihydrotestosterone, estrone, and estradiol could not be detected in the media. Luteinizing hormone (LH) alone significantly increased P and delta 4 A accumulation. Insulin alone increased P accumulation on days 2 to 4 of culture. Insulin alone did not stimulate delta 4 A accumulation. Insulin plus LH resulted in a significantly greater accumulation of P and delta 4 A than LH alone. These results suggest that insulin may be a regulator of ovarian thecal steroidogenesis.

Androstenedione↗